We have recently shown that the development of neoplasia in mice following graft versus host reactions (GVHR) or skin transplantation appears to be a result of interactions among immunostimulation, oncogenic virus activation, and immunosuppression. One obective is to further explore these complex interactions in the above mentioned mouse model systems as well as in mixed mouse lymphocyte cultures (MLC) in vitro. We will attempt to determine in these situations the mechanisms of activation, the time and site of viral release, and the effects of anti- viral agents on both viral activation and oncogenesis. A second major objective is to extend these observations to analagous human immunological disorders. We will examine transplanted renal tissue obtained at the time of a graft rejection crisis for the presence of both oncogenic and non-oncogenic viruses by classical virological isolation techniques as well as by more recent methods for detection of oncogenic viruses. We will also explore the pathogenesis of cytomegalovirus-induced post-transfusson mononucleosis by determining whether cytomegalovirus can be activated by mixed lymphocyte cultures between appropriately selected human cell populations. A third objective is to further define the mechanisms underlying the virus carrier state following neonatal or congenital virus infections with murine leukemia viruses, using sensitive assays for cell-mediated cytotoxicity and blocking antibody.